CSL312 Safety, Pharmacokinetics, and Pharmacodynamics in IPF
Research type
Research Study
Full title
A Randomized, Double-blind, Placebo-controlled, Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of CSL312 in Subjects with Idiopathic Pulmonary Fibrosis
IRAS ID
305919
Contact name
Nazia Chaudhuri
Contact email
Sponsor organisation
CSL Behring LLC
Eudract number
2021-003162-12
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 7 months, 2 days
Research summary
Research Summary
This study aims to assess the safety and efficacy of a treatment for Idiopathic pulmonary fibrosis (IPF). This is a condition in which the lungs become scarred and breathing becomes increasingly difficult. Several treatments can help reduce the rate at which IPF gets worse, but there's currently no treatment that can stop or reverse the scarring of the lungs. In people with IPF, the tiny air sacs in the lungs (alveoli) become damaged and increasingly scarred. This causes the lungs to become stiff and means it's difficult for oxygen to get into the blood. CSL312 is a new drug that blocks the activity of a blood clotting factor called Factor XIIa. CSL312 may be able to decrease production of substances that cause the inflammation and fibrosis that lead to scarring of the lungs.
Approximately 80 subjects will take part in the study at approximately 50 sites.
This study will focus on safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the study drug in patients by measuring the levels of study drug in the blood and to see how well it is tolerated.Summary of Results
Participants were in the study for up to 6 months. Entire study took 2 years to complete . Study started Jan 2022 and ended Jan 2024.The study had 81 participants in 11 countries. The UK had a total number of 8 participants. The research was conducted because researchers are looking for a better way to treat IPF (Idiopathic Pulmonary Fibrosis ) in adults. IPF is a lung disease where the tissue in the lungs become thick and scarred over time. In turn this makes it hard for people to breathe and get enough oxygen into their blood. The causes of IPF are unknown and there is no cure. Disease gets worse over time, leading to serious breathing problems.
The study drug garadacimab is designed to work by blocking a certain protein in the body that is believed to play a role in making the lung tissue scarred and thick. If garadacimab can slow down this scarring, it might help people with IPF breath more easily and live longer. In this research we wanted to find out if the participants had any medical problems that might be related to garadacimab. They also wanted to find out how garadacimab moved through the blood and affected other blood test results related to IPD, but this was not one of the main questions in this study, so it is not included in this summary. The main questions for this study were :
• How did the participants overall health change during the study ?
• What possible related medical problems did participants have during the study ?
In total the study included 46 males and 35 females.
The participants could join the study based on the following:
-They had IPD
-They were 40 years of age or older
-They didn’t have any other significant medical problems that would make participating in the study risky or dangerous for them.
The participants in this study received either garadacimab or a placebo. A placebo looks like a drug but does not have any medicine in it. Researchers use a placebo to help make sure any of the effects they see in the participants who receie the drug are caused by the drug.
This was a double-blind study, which means none of the participants, doctors or other study staff knew what treatment each participant received. CSL Behring was provided information about which treatment participants received so they could create a report of the study results. A computer program was used to randomly choose the treatment each participant received. Thia makes sure the groups are chosen fairly. As a result, 40 participants were on garadacimab and 41 on placebo.
Doses were given as follows:
-Dose 1 (Week 1)- given through needle directly into a vein (intravenous infusion ) -Doses 2,3,4 (given every 4 weeks starting on Week 2 )were given as an injection just under the skin -subcutaneous .
The results for each participant vary from the overall summary of results. Once the full results are available these will be made available on other websites.
The overall results of this study showed that when tested and measured the participants health had small changes. This was based on measuring their blood samples and heart health. These small changes were deemed not meaningful.
4 participants developed anti-drug antibodies which are proteins made by the immune system to find and fight off anything the body does not recognize. The patient consisted of 2 in the garadacimab and 2 in the placebo group.
The participants who developed anti-drug antibodies whilst on placebo could have had these even if they didn’t take garadacimab. This could happen by chance. The tests the researchers used may sometimes count antibodies that formed against other drugs. Lastly sometimes the tests used by researchers can give a false positive. The study doctors kept track of the adverse events that the participants had. An adverse event is any medical problem that a participant has during the study. These problems can be directly or indirectly linked to the study drug. An adverse event is considered serious if its life threatening, causes lasting problems, is medically significant, requires hospital care or results in death.
5 patients who were in the garadacimab group developed a serious adverse event. Including one patient that had to stop participating in the study.
26 had adverse events. The most common serious adverse event was a worsening of idiopathic pulmonary fibrosis. The most common adverse event – diarrhoea, cough, dizziness and fatigue. Other studies with garadacimab showed that participants in those studies had specific adverse events. The researchers wanted to check if the adverse event were like the ones that were previously reported, these are called Adverse events of special interest-AESIs In this study there were 2 patients that had AESIs. These were on garadacimab. Most common AESIs were nose bleeds, coughing up blood and death of brain tissue from lack of blood flow.
Finally, the study helped researchers learn more about garadacimab in people with idiopathic pulmonary fibrosis. Researchers look at results of many studies to decide with treatments work best and are safety for patients. This summary shows only the main results from one study. Other studies may provide new information or different results. Further clinical studies with garadacimab in adults with IPF are currently not planned.REC name
Yorkshire & The Humber - Leeds East Research Ethics Committee
REC reference
21/YH/0290
Date of REC Opinion
17 Jan 2022
REC opinion
Further Information Favourable Opinion